Jugg B, Jenner J, Hughes J N, Rice P
BioMedical Sciences Department, Chemical and Biological Defence Sector, Salisbury, Wiltshire, UK.
Hum Exp Toxicol. 2001 May;20(5):267-76. doi: 10.1191/096032701678227686.
Hexafluorocyclobutene (HFCB), a reactive organohalogen gas, causes overwhelming pulmonary oedema. We investigated its effect on the rat lung surfactant system, comparing its action on type II pneumocytes with air-exposed rats. The inflammatory cell population and protein content of bronchoalveolar lavage fluid was analysed following exposure to air or HFCB (LCt30). Six rat lung phospholipids were measured by high-performance liquid chromatography, following solid phase extraction (SPE) from lavage fluid. Transmission electron microscopy (TEM) was used to visualise effects on alveolar type II cell ultrastructure. HFCB caused changes in cell populations and increased lavage fluid protein compared to controls, suggesting a permeability oedema. Changes in the total amount and percentage composition (sustained decrease in phosphatidylglycerol and phosphatidylcholine) of surfactant phospholipids also occurred. TEM observations indicated no direct ultrastructural damage to the type II cells, but showed initial, rapid release of surfactant into the alveolar space. HFCB altered the surfactant system in a manner similar to that shown following another reactive organohalogen gas, perfluoroisobutene (PFIB), but differently to that after phosgene. These differences suggest different mechanisms of action even though pulmonary oedema is the final injury for all gases. Better knowledge of the mechanisms involved will improve prospects for prophylactic/therapeutic intervention.
六氟环丁烯(HFCB)是一种活性有机卤代气体,可导致严重的肺水肿。我们研究了它对大鼠肺表面活性物质系统的影响,将其对II型肺细胞的作用与暴露于空气中的大鼠进行比较。在暴露于空气或HFCB(LCt30)后,分析支气管肺泡灌洗液中的炎性细胞数量和蛋白质含量。从灌洗液中进行固相萃取(SPE)后,通过高效液相色谱法测量六种大鼠肺磷脂。使用透射电子显微镜(TEM)观察对肺泡II型细胞超微结构的影响。与对照组相比,HFCB导致细胞数量发生变化,并使灌洗液中的蛋白质增加,提示存在通透性水肿。表面活性物质磷脂的总量和百分比组成也发生了变化(磷脂酰甘油和磷脂酰胆碱持续减少)。TEM观察表明,II型细胞没有直接的超微结构损伤,但显示表面活性物质最初迅速释放到肺泡腔中。HFCB对表面活性物质系统的改变方式与另一种活性有机卤代气体全氟异丁烯(PFIB)相似,但与光气不同。这些差异表明,即使肺水肿是所有气体造成的最终损伤,其作用机制也有所不同。更好地了解其中涉及的机制将改善预防/治疗干预的前景。